Injection device for soft-tissue augmentation fillers, bioactive agents and other biocompatible materials in liquid or gel form

ABSTRACT

Described herein are injection devices capable of automatically injecting substances into the soft tissue of a patient. The devices can inject low to high viscosity materials at predetermined, user selected injection rates, allowing the operator more control than a traditional syringe. The devices can allow mixing of more than one substance and/or reconstitution of a solid substance for injection. The injection devices described herein can allow the operator to easily inject one or more low to high viscosity liquid or gel soft-tissue augmentation fillers, one or more drugs, one or more other biocompatible materials, or combinations thereof.

RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.15/366,824, filed Dec. 1, 2016, which is a continuation of U.S. patentapplication Ser. No. 14/316,649, filed Jun. 26, 2014, which is acontinuation of U.S. patent application Ser. No. 12/994,568, filed Jan.24, 2011, now issued as U.S. Pat. No. 8,801,659, which is a nationalstage application under 35 U.S.C. § 371 of PCT Application No.PCT/US2009/045831, filed Jun. 1, 2009, which claims the benefit of U.S.Provisional Patent Application No. 61/057,703 filed on May 30, 2008, andU.S. Provisional Patent Application No. 61/074,538 filed on Jun. 20,2008, the entire disclosure of each of these applications beingincorporated herein by this reference.

FIELD OF THE INVENTION

The present invention relates to devices useful for injectingsoft-tissue augmentation fillers, bioactive agents and otherbiocompatible materials.

BACKGROUND OF THE INVENTION

The injection of bioactive agents and tissue augmentation fillers isquite commonplace. Commonly, bioactive agents and tissue augmentationfillers are injected manually using traditional hypodermic syringes withmanual plungers. One monumental problem with traditional syringes isthat they are difficult to properly utilize due to their poorergonomics.

Another problem commonly encountered when using hypodermic syringes withmanual plungers is the difficulty of controlling the rate of injection,especially when the injectable substance is highly viscous, the tissuebeing injected into is dense or a combination of the two. In such cases,the force required to extrude the injectable substance into a patientmakes controlling the rate of injection and the handling of the syringestrikingly difficult. Commonly, unreliable injection speeds areencountered as well as patient pain associated with additional axialforce on the syringe in an effort to supply sufficient extrusion forceto the syringe's plunger to force the injectable substance out of theneedle into the patient's tissues.

Another problem with injectable substances relates to reconstitutionprior to injection. Certain substances need to be reconstitutedimmediately prior to injection. Patient discomfort with injections canlie in anticipation of the injection itself, and therefore, lead to atense patient and hence more discomfort upon injection. As such,manually reconstituting an injectable just prior to injection can causeboth mental and physical discomfort for a patient. A device that canautomatically reconstitute injectables within the device itself justprior to injection would be a promising technology.

SUMMARY OF THE INVENTION

Accordingly, hand-held injection devices for soft tissue are provided.In an exemplary embodiment of the invention, an injection device isprovided which generally comprises a cartridge suitable for containingan injectable material and couplable to a needle, a body or shellstructured to contain the cartridge, a drive mechanism including a motorand a piston for moving the injectable material from the cartridgethrough the needle, a power source, for example a battery contained inthe shell, for activation the drive mechanism; and a user programmablecontroller coupled to the drive mechanism, where a user-definedinjection rate can be set. Advantageously, in this exemplary embodiment,the device is capable of injecting the injectable material at the userdefined injection rate from the cartridge and through the needle at aforce of up to about 50 Newtons (N), for example, up to 100 N, forexample, up to 200 N or more. The cartridge may be substantiallycylindrical in shape and may have an inner diameter of between about0.25 inch to about 1 inch, or between about 0.18 inch to about 0.35inch.

Further, the device is structured to be capable of delivering, orinjecting, precisely defined volumes of materials, for example,relatively high viscosity materials, such as dermal fillers, at saiduser-defined injection rates. For example, the device is especiallyadvantageous for enabling controlled injection of precise volumes ofcrosslinked hyaluronic acid based dermal fillers into soft tissue at asubstantially constant rate.

In some embodiments, the device is structured as a self-contained,handheld device which requires no external wiring, external powersource, conduits nor other external components for operation. The deviceconveniently requires only single hand operation and is sufficientlylightweight so as to be easily maneuverable by a physician.

Advantageously, many of the present devices are structured to providehighly controlled, precisely quantified injection of materials throughvery fine needles, wherein such materials are extremely difficult toinject, or even impossible to inject, using conventional techniques andmanually operated syringes.

The controller may be configured to be capable of allowing a user to seta predefined, user-selected, injection rate for the material. A range ofinjection rates available for selection may be, for example, anyinjection rate defined between about 0.001 mL/sec and about 1 mL/sec. Inaddition, the injection device is capable of injecting the material atthe user defined injection rate through a needle having a gauge of atleast about 10 G and up to about 50 G, for example, a needle having agauge between about 23 G to about 34 G, for example, between about 27 Gto about 32 G. The needles may have a length of between about ¼ inch toabout 2 inches, or between about ½ inch to about 1½ inches.

For example, many of the devices in accordance with the invention aredesigned to allow the user, for example, physician, to easily injectprecise amounts of low to high viscosity liquids or gel soft-tissueaugmentation fillers, one or more bioactive agents, one or more otherbiocompatible materials, or combinations thereof (hereinafter sometimes,collectively referred to as “injectable material”) at pre-selectedinjection rates.

In another aspect of the invention, methods are provided for injectingmaterials, for example, viscous materials such as dermal fillers, into asoft tissue of a patient. In one embodiment, a method for injecting amaterial into soft tissue is provided which generally comprises thesteps of providing a motorized injection device having a needle,providing a cartridge containing a dermal filler material to be injectedinto soft tissue of a patient, programming a user-defined injection rateof the material into the device, inserting the cartridge into thedevice, and using the device to inject the material from the cartridgeand through the needle and into the soft tissue of the patient at theprogrammed injection rate. Advantageously, the device may be structuredto be capable of injecting the injectable material at the user-definedinjection rate at a force of between about 50 Newtons to about 200Newtons or greater.

In yet another aspect of the invention, a method of injecting a materialinto soft tissue is provided, wherein the method comprises the steps ofproviding a motorized injection device containing a first material and asecond material separated from the first material, and, within thedevice, mixing the first material with the second material to create aproduct to be injected into soft tissue of a patient. The method furthercomprises programming a user-defined injection rate of the product intothe device and using the device to inject the product into the softtissue of the patient at the programmed injection rate. In a specificembodiment, the first material is a dry material, for example, a powderor lyophilized material and the second material is a liquid, forexample, saline, a solvent or a liquid suitable for reconstituting thefirst material.

In one aspect of the invention, the injectable material is selected fromthe group consisting of dermal fillers, hyaluronic acid-based dermalfillers, hydrogels, organogels, xerogels, encapsulated and/orcross-linked biomaterials, silicones, glycosaminoglycans,polysaccharides, collagen, elastin, local anesthetics, drugs, bioactiveagents, antioxidants, enzyme inhibitors, vitamins, minerals, water,saline, light curable or light activated materials, pH curable or pHactivated materials and botulinum toxin.

In one embodiment, the soft tissue is selected from the group consistingof skin, muscles, glands, ducts, tendons, follicles, and combinationsthereof. In another embodiment, the skin is located on an area selectedfrom the group consisting of face, neck, arms, underarms, legs,buttocks, abdomen, back, breasts, scalp, feet, and hands.

In one embodiment, a method is described for injecting a solid bioactiveagent into a soft tissue comprising: providing an injection devicecomprising an inner body, and outer body and a needle; providing a solidto be injected into the patient wherein the solid is housed within theinner body of the device; mixing the solid with a solvent therebyreconstituting the solid and forming a product to be injected; and usingthe device to inject the product through the needle into the patientwith an extrusion force great enough to deliver the product to the softtissue at a rate programmed into the device before injection.

In one embodiment, the injectable material is selected from the groupconsisting of dermal fillers, hyaluronic acid-based dermal fillers,hydrogels, organogels, xerogels, encapsulated and/or cross-linkedbiomaterials, silicones, glycosaminoglycans, polysaccharides, collagen,elastin, local anesthetics, drugs, bioactive agents, antioxidants,enzyme inhibitors, vitamins, minerals, water, saline, light curable orlight activated materials, pH curable or pH activated materials andbotulinum toxin.

DEFINITION OF TERMS

Digits: As used herein “digits” shall refer to the fingers of a human.Each digit or finger can be referred to separately or in combination.Digit 1 is commonly referred to as the thumb. Digit 2 is commonlyreferred to as the index finger. Digit 3 is commonly referred to as themiddle finger. Digit 4 is commonly referred to as the ring finger. Digit5 is commonly referred to as the pinky finger.

BRIEF DESCRIPTION OF THE DRAWINGS

Many of the advantages and features of the present invention may bebetter appreciated and more clearly understood with reference to thefollowing detailed description and the accompanying drawings of which:

FIGS. 1A, 1B and 1C are perspective, top and side views, respectively,of an embodiment of a programmable injection device in accordance withthe invention;

FIGS. 2A and 2B are perspective views of another embodiment of theinvention.

FIG. 3 is a perspective view of yet another embodiment of the invention;

FIG. 4 shows a display screen of an injection device of any of theembodiments shown in FIGS. 1A-4;

FIG. 5 shows a simplified side view of internal components of the deviceshown in FIGS. 1A-1C, an outer shell of the device removed for clarity;

FIG. 6 is a simplified perspective view of internal components of anembodiment of the invention which allows for mixing different materialsprior to injection into soft tissue;

FIG. 7 is a simplified perspective view of some of the internalcomponents of yet a still further embodiment of the invention;

FIGS. 8A and 8B show top and side views of another embodiment of theinvention;

FIG. 9 depicts a logic/block diagram of some of the internal componentsof any of the embodiments shown elsewhere herein;

FIG. 10 depicts various examples of possible display screens of any ofthe injection devices shown elsewhere herein; and

FIG. 11 depicts a non-limiting combination of components housed in aninner body of a device of the invention, for example, the device shownin FIGS. 8A and 8B.

DETAILED DESCRIPTION OF THE INVENTION

Described herein are novel injection devices that allow a user, forexample, a physician, to inject one or more low to high viscosity liquidor gel soft-tissue augmentation fillers, one or more bioactive agents,one or more other biocompatible materials, or combinations thereof in aprecisely controlled manner. In some embodiments, the present devicesallow the injection of materials that are difficult or impossible toinject with a traditional manual hand held syringe.

The devices described herein allow the operator to easily inject amaterial through any size needle known in the art by depressing abutton. The devices are easy to hold, manipulate and operate with onehand, and in some cases adjust easily with the operator's opposing hand.The devices allow the operator to set a precise injection speed orextrusion rate of the material to be injected. The devices can alsoindicate the initial volume, volume injected and remaining volume of thematerial being delivered to a patient.

In one embodiment, the devices are comprised of an outer shell and aninner body. The inner body houses one or more user-replaceablecartridges, one or more internal drive mechanisms and any other internalmechanisms described infra.

The devices can conceivably be used to inject an injectable materialinto any suitable location of a patient's body. In one embodiment, thedevices described herein are used to inject materials into the patient'ssoft tissue. In a further embodiment, the soft tissue is the patient'sskin. In other embodiments, the soft tissue can be muscles, glands,ducts, tendons, follicles, and the like. The device can be used toinject materials into, for example, the face, neck, arms, underarms,legs, buttocks, abdomen, back, breasts, scalp, feet and/or hands.

The Outer Shell

The devices described herein comprise an outer shell. The outer shellhas an ergonomic shape that facilitates manipulation of the device.Additionally, the present devices can accommodate operator hands ofdifferent sizes. Hand size accommodation can be accomplished bydifferent device sizes, position-adjustable device handgrips orinterchangeable device handgrips. For example, interchangeable devicehandgrips can come in various predetermined sizes or can be personalizedfor a particular user. In one embodiment, the device handgrip can slidealong a rail forward or backward relative to the outer shell and belocked into place. In another embodiment, the device handgrip can beunlocked, removed and re-attached in another position on the outershell.

Four exemplary, outer shell shapes suitable for use as part of thepresent devices are depicted in FIGS. 1-3 and 8.

FIGS. 1A, 1B and 1C depict three different views of a device 100 inaccordance with an embodiment of the invention. Device 100 is a somewhatpen style design. Device 100 includes a shell 101 structured to be heldby the operator in a similar manner to that of a writing instrument.Device 100 is held such that the operator's thumb may be positioned in afinger grip 102, the index finger is positioned such that it may engageinject button 102A and/or 102B and injector speed adjustment buttons 103and/or 104. The weight of device 100 rests on the middle finger and thehand between the thumb and index finger. The device 100 can be used byboth right and left handed operators as there are mirrored finger grips102 and injection buttons 102A and 102B on both sides of the device 100.It can be appreciated that with suitable modification to device 100within the scope of the invention, device 100 can be designed to bespecifically used by a right handed operator. Similarly, the device 100can be modified within the scope of the invention to be specificallyused by a left handed operator.

The device 100 is powered on and off using power button 105. The devicefurther comprises a display 106 to provide information about the devicefor reference by the operator. The information on display 106 can beadjusted using menu driven multibutton 108 and confirmed using button109.

A cartridge (not shown in FIGS. 1A, 1B and 1C) containing material to beinjected can be installed into the device 100 by removing end cap 107,inserting cartridge into shell 101 and reinstalling end cap 107. Thecartridge is couplable to a needle 112 by means of a luer tip 113.

FIGS. 2A and 2B depict another device 200 in accordance with theinvention which may be substantially the same as device 100 with theexception of the shape of the shell 201. Shell 201 is shaped togenerally conform to a finger of the user/operator. In one embodiment,the finger is an index finger (digit 2). The top of the device 200 has adepression 202 for the index finger to fit comfortably on device, withan injection button 203 situated to be located at the end of the finger.The thumb (digit 1) and the middle finger (digit 3) can be placedcomfortably against the two opposing sides of such a device to aid incontrol. However, it is conceivable that such a device can be operatedusing any finger (digit 1-5) the operator feels comfortable with and anycombination of other fingers used for supporting the device. Theproximal end of the device comprises a “U” shaped appendage 204 whereinthe finger is inserted and which rests on the hand at the base of thefinger. The appendage 204 can be constructed of a flexible materialwhich can be formed to the particular operator's finger length andcircumference. Finger length accommodation can be accomplished byphysically different device sizes or adjustable device lengths and/orwidths. The device can also comprise a side window 205 and/or a bottomwindow 206, running the length of the bottom side of the device 200.

FIG. 3 depicts another embodiment of the invention, for example, whereina shell 301 of the device 300 has a pistol-grip style design. Device300, which is held firmly in an operator's hand using finger grips 302.Digits 2-5 can fit snugly into finger grips 302. Digit 1 can remain freeto engage inject button 303. The shell 301 may comprise a window oradditional opening wherein the operator can view the volume of theinjectable material in the cartridges.

FIGS. 8A and 8B depict another device 800 in accordance with theinvention. Device 800 comprises shell 800 a including handle 801. Injectbuttons 802 and/or 803 can be engaged by the index finger of theoperator, the button used depending on which is most comfortable to usefor the operator, for example, depending upon whether the operator isright or left handed. Eject button 804 is easily operated by either aright or left handed user (a similar button is located on the oppositeside of the device) to eject the cartridge (not shown). A power/menubutton 805 can be provided to control the power to the device by holdingbutton 805 down or can operate menus displayed on display 806 andadjusted by selector button 807. Needle 808 is connected to cartridge809 via a luer style connection which, in one embodiment, can insertedinto the device 800 through the front of the device and snapped intoplace within the device 800, similar to that of the device 100 shown inFIGS. 1A-1C.

The shells 101, 201, 301, 800 a of devices 100, 200, 300 and 800respectively, can be comprised of any suitable materials such as, butnot limited to, rigid thermoplastics, thermoplastic elastomers,silicones, glass, metals, composite materials, carbon fillers, or anycombination thereof.

Depending on the particular application, it may be desirable for thedevices 100, 200, 300, 800 to be routinely sterilized by means commonlyknown in the art. Therefore, the components of the devices may be madeof materials that are known to withstand sterilization techniques suchas, but not limited to, dry heat, steam (autoclave), ethylene oxidetreatment, gamma radiation, ultra violet (UV) light or combinationsthereof including other methods known in the art. The devices can alsobe constructed of materials that can be cleaned with soap and water orantiseptic materials.

The shells 101, 201, 301, 800 a may include one or more variousergonomic features such as detents, depressions and/or extrusions. Thefeatures further allow the devise to be easily held, manipulated andoperated with one hand, or if necessary, adjustments can be made withthe opposing hand. In one aspect of the invention, each of devices 100,200, 300 and 800 can be structured to be substantially entirelyself-contained, requiring no external power source, conduits or otherexternal components for operation.

In addition to, or in lieu of the button functions already hereindescribed, button functions may include, but are not limited to, power(to turn the device on and off), inject (to inject the injectablematerial), eject (to eject a cartridge), adjustment (for injection speedor rate), menu (for electronic display screen), adjustment (electronicdisplay screen menu options), set/accept/enter (to accept an adjustmentin a menu) and combinations of button described herein.

In some embodiments, an inject button coupled to a pressure sensitiveswitch is provided in order that the delivery rate of the material maybe adjusted based on the amount of pressure a user applies to the injectbutton.

In addition, it is contemplated that the outer shell of the devices mayhave one or more light emitting devices to indicate states of theinjection device. In one embodiment, the light emitting device is alight emitting diode (LED). The LEDs can be used to indicate status ofthe device and can be of different colors to indicate different stagesof readiness. Some non-limiting examples include an LED which is red toindicate that the device is not ready or green to indicate the device isready. Additionally, a yellow LED can be used to indicate that thecartridge is low and needs replacing.

Each device described herein may have at least a portion sealed toprevent fluids or debris from entering the inner body of the device.Methods of sealing a medical device of this type are known in the artand can include, but are not limited to, o-rings, gaskets, sealants,silicones, thermoplastic elastomers, polymers, polymer coatings,sheaths, partial sheaths and waxes. The external buttons described supramay be sealed to prevent fluids or debris from entering the inner bodyof the device through the buttons location.

The devices may further comprise an electronic display screen, such asdisplay 106 shown in device 100 in FIGS. 1A-1C and display 806 shown indevice 800 in FIG. 8A. Screens can include those commonly known in theart that are easily viewable by the operator including, but not limitedto, organic light-emitting diode (OLED), light emitting diode (LED) orliquid crystal display (LCD). The display screen can display informationabout the device, about the cartridge, about the injectable materialand/or about the injection itself. The screen can display some or all ofthe following, non-limiting, example information: company name and/orlogo, device name, injectable material name and/or logo, device partnumber, injectable material (i.e. Product) part number, Productreference number, device lot number, Product lot number, Product volume,Product expiration date, cartridge volume, initial Product volume,remaining Product volume, Product volume injected into a specificanatomy of the patient, Product injection speed, depth of injection,needle force, needle gauge, needle length, patient name, patientidentification, location of injection (patient's anatomy), date, time,language, number of uses or injections (until battery needs rechargingor replacement), device status (e.g. ready, cartridge not loaded,cartridge empty, error), firmware version, power status (on, off,standby), battery power, battery power remaining, and/or batterycharging status.

The information displayed on the screen may be displayed on the primarymenu screen or on one or more user-selectable or user-configurable menuscreens. The operator may easily customize the screen. The electronicdisplay screen and operating system may be software or firmwareupgradeable by any means known in the art.

FIG. 4 depicts an exemplary display screen. Display screen 400 candisplay information such as, but not limited to, injectable material(e.g. Product) expiration date 401, volume of Product remaining 402,starting volume 403, injection speed 404, and battery power indicator405. There are several other possible screen configurations andinformation that can be displayed on the screen. One skilled in the artmay envision other possible configurations and pieces of informationthat may be useful on the screen and those configurations and pieces ofinformation are considered within the scope of the present description.

The Inner Body

The inner body of the devices 100, 200, 300, 800 may comprise one ormore of the following components used to inject the injectable materialinto soft tissue in a patient from the cartridge through the needle:vacuum pump, air pump, motor (e.g. gear or step motor), gears (e.g. rackand pinion system or worm gear), linear actuator, linear spine shaft,linear guide, air piston(s), springs (e.g. compression), magnets and/orreplaceable compressed air cartridge.

The inner body can comprise one or more motors or actuators to moveinternal components. The motor(s) and/or actuator(s) can drive one ormore gears and can be driven by an appropriate voltage. The motor canhave a maximum stall torque of 7,500 g cm, 5,000 g cm, or 4,480 g cm.The stall torque can have a minimum of 100 g cm, 250 g cm, or 396 g cm.The maximum efficiency torque can have a maximum of 1,500 g cm, 1,000 gcm, or 900 g cm. The maximum efficiency torque can have a minimum of 50g, 75 g cm, or 88 g cm. Further, the gear ratio of the motor and/oractuator can have a maximum of about 500:1, 350:1, or 300:1. The gearratio of the motor and/or actuator can have a minimum of about 10:1,25:1, 30:1, or 100:1. In one embodiment, the gear ratio can be about298:1. In one embodiment, the motor is a Firgelli GM12-N2OVA-08260-298-Rgear motor (Firgelli Technologies, Inc. Victoria, BC, Canada).

FIG. 5 is an exemplary, non-limiting, configuration 500 of variouscomponents which may form part of device 100 shown in FIGS. 1A-1C, withhousing 101 removed for the sake of clarity. Device 100 may comprise,for example, cartridge 507 couplable to needle 508, and motor 501 whosedriveshaft is fitted with a first gear 502. First gear 502 drives secondgear 503. One skilled in the art will appreciate that there are severalgear/motor combinations which can be used to achieve various lineardrive speeds. In one embodiment, the device may comprise one or moreworm gears. Second gear 503 drives rack 504 which engages plunger 505.Plunger 505 is driven by rack 504 through cartridge 507. As plunger 505is driven through cartridge 507, the injectable material 506 is forcedout of needle 508.

In some embodiments of the invention, device 100, 200, 300 and 800 caninclude features enabling the device to mix different materials,products and medicaments, or medicaments within the device and prior toinjection. In one embodiment, the injectable material includes a solidor dry component, for example, a lyophilized component, and a liquidcomponent, for example, a solvent such as saline for reconstituting thedry component prior to injection. In such a case, additional componentsof the device may be included. These include, but are not limited to, avacuum pump, an air pump, a gear and/or step motor, one or more gears, alinear actuator, a linear spine shaft, a linear guide, an air piston,one or more springs, one or more magnets, and replaceable aircartridges.

For example, FIG. 6 is a simplified perspective view of internalcomponents 600 of an embodiment of the invention which allows for mixingdifferent materials prior to injection into soft tissue. It should beappreciated that any of devices 100, 200, 300 or 800 can be constructedwithin the scope of the invention to include internal components 600which allows for mixing of materials prior to injection. Components 600may include, for example, a miniaturized motor 601 including driveshaftfitted with a first gear 602 which drives second gear 603. One skilledin the art will appreciate that there are several gear motorcombinations which can be used to achieve various linear drive speeds.In one embodiment, the device may comprise one or more worm gears.Second gear 603 drives rack 604 which engages plunger 605. Plunger 605is driven by rack 604 through cartridge 607. A vial 608 of a secondmaterial can be attached to a pump 699, wherein the pump directs thesecond material through a one way valve 610 and into cartridge 607. Thefirst material and the second material are mixed in cartridge 607.Cartridge 607 can be agitated by a vibration from a second motor 611fitted with a weight 612. As the weight, which is out of balance, spins,the device vibrates agitating the mixture in cartridge 607. Plunger 605is driven through cartridge 607, and the Product 606 is forced out ofneedle 613.

The second material can be substance used to dilute, dissolve orsaturate the first material. In one embodiment, the second medicament issaline. In another embodiment, it is water. In one embodiment, it is anyappropriate solvent to dissolve a solid, free-dried, freeze-dried,lyophilized, frozen, or aspirated product, or combinations thereof.

The inner body of the devices may contain microelectronics, for example,at least one printed circuit board (PCB) to control electronic functionsof the device. The PCB can control the display screen, pump, motor,linear actuator and/or other powered components. The PCB can be used toregulate the current and/or voltage delivered to the various electronicparts of the devices.

In one non-limiting embodiment, the internal components may comprise amotor as described above attached to a worm gear which drives a rack.The motor, an LCD display, microswitch, insertion/ejection mechanism,and optical encoder may all be controlled by a PCB. The PCB may bepowered by a battery located adjacent to the PCB.

In one embodiment, the at least one cartridge housed in the inner bodyof the device maybe be ejected manually, automatically, orsemi-automatically. Automatic methods can be devised using one or moreof the following, non-limiting components: motor (e.g. gear or stepper),gears (e.g. rack and pinion, worm or worm gear), linear actuator, airpiston, springs (e.g. compression or extension) and/or magnets.

The devices described herein may contain a force or strain gauge used tomeasure the puncture force and depth of the needle through the patient'sskin. The depth of the injection can be important for certain types ofProducts and their respective absorption rates. The puncture force canbe instrumental to reducing injection pain as it can serve to adjust theforce of the needle puncture depending on the skin type and needlegauge.

In one embodiment, the devices described herein comprise a linearvariable differential transformer (LVDT). An LVDT can be used to measureliner displacement. The LVDT can be used to measure the depth of theneedle through the patient's skin or tissue or can be used to measurethe depth of the plunger into the cartridge, thereby measuring theamount of Product dispensed from the device.

The devices described herein may comprise a temperature controlled unit.The unit can comprise a jacket that surrounds the cartridge therebyallowing the operator to keep the Product either heated or cooledbefore, during, and between injections. This may be more critical forsome Products more than others, for example, Products that must be keptrefrigerated would benefit from this technology.

The Cartridge

The devices 100, 200, 300, 800 can comprise one or more cartridges, forexample, cartridge 507 and 607 shown in FIGS. 5 and 6 respectively, forcontaining an injectable material. The cartridge can comprise anysuitable material of construction, for example, a rigid thermoplastic,thermoplastic elastomer, silicone, glass, metal, composite materials orany combination thereof. The cartridge can have an outer diameter ofabout 1/16 inch to about 1 inch. The cartridge may have an innerdiameter of about 1/16 inch to about ⅞ inch. The length of the cartridgecan be from about ½ inch to about 6 inches.

The cartridge can accommodate material volumes from about 0.1 mL toabout 60 mL, more preferably, about 0.1 mL to about 10 mL. The cartridgecan contain a specific or predetermined amount of material to bedelivered to a patient. The cartridge can have a luer-tip or slip-tipend (both commonly seen on ordinary medical syringes). An example of aluer-tip end can be seen in FIG. 5.

The cartridge can have various outer cross section designs and the innerbody chamber may be designed to accommodate the designs. The outer crosssection design can be selected from the following non-limiting examples:round, elliptical, rectangular, square, or polygon in shape. In apreferred embodiment, the cross section design is round. In someembodiments, the cartridge is substantially cylindrical in shape and hasan inner diameter of between about 0.25 inch to about 1 inch, or betweenabout 0.18 inch to about 0.35 inch.

In one embodiment, the cartridge has a unique shape to be used only withone of the devices described herein.

The cartridge can have a protruding or snap feature used to lock thecartridge into the inner body of the devices when it is fully inserted.This feature can also be a protruding or snap feature found on the innerbody of the devices.

The cartridge can comprise a needle or is structured to be couplable toa needle. The needle may be integrated or may be an interchangeableneedle. In some embodiments, the device is structured to inject materialat a user defined injection rate through a needle of at least about 10G, for example, between about 23 G and about 34 G, for example, betweenabout 27 G and about 32 G. The length of the needles used can be anyappropriate length known in the art, for example, the needle may have alength of between about 1/16 inch and about 3 inches, for example,between about ¼ inch to about 2 inches, for example, between about ½inch to about 1½ inches.

The cartridge may further comprise a one-way valve. The one-way valvemay comprise an adjustable orifice used to regulate the speed or forceof material being injected. This one way valve may be adjustablemanually or electronically, controlled by the printed circuit board(PCB) found in the inner body.

The cartridge can comprise an electronic identification tag affixed tothe outside of the cartridge. In one embodiment, the electronicidentification tag is a radiofrequency identification (RFID) tag. Theinformation contained in the RFID tag can be processed by aradio-frequency reader housed in the inner body of the devices. As such,the RFID tag can contain and relay specific information to the deviceswhen the cartridge is inserted. Exemplary information that can be storedon an RFID tag include, but is not limited to, Product name, Productreference number, Product part number, Product prescription (Rx) number,Product lot number, Product volume, Product expiration date, Productefficacy, Product concentration and/or Product weight. The informationprocessed by the device can be displayed on the electronic displayscreen and/or stored in the device itself.

The cartridge can comprise one or more external features, such asridges, detents and/or depressions. The external features allow thecartridge to be read and identified by optical encoder(s) and/ormicroswitch(es) that are housed in the inner body of the devices.Exemplary information that can be identified using external featuresinclude, but is not limited to, Product name, Product reference number,Product part number, Product Rx number, Product lot number, Productvolume, Product expiration date, Product efficacy, Product concentrationand/or Product weight. The information processed by the device can bedisplayed on the electronic display screen and/or stored in the deviceitself.

A dual chamber cartridge is depicted in FIG. 7. One skilled in the artwill understand that a multi-chamber cartridge is not limited to twochambers, but rather can have three or more. Multi-chamber cartridge 700comprises at least two plungers. The first chamber 703 can be filledwith a bioactive agent, a solvent, or any other appropriate fluid.Plunger 701 is advanced through chamber 703 thereby advancing thecontents of chamber 703 into plunger 702 and thereby advancing plunger702 to channel 707. Once plunger 702 reaches channel 707, the contentsin chamber 703 are allowed to pass through channel 707 into chamber 704.The speed that the contents of chamber 703 are passed through channel707 can be monitored and the force applied to plunger 701 can beadjusted to advance it at an appropriate rate. Chamber 704 can be filledwith a bioactive agent, a solvent, or any other appropriate fluid. Inone embodiment, chamber 704 can be at least partially filled with asolid form of a bioactive agent 705 which needs to be reconstituted. Asplunger 701 advances toward plunger 702, the contents of chamber 703 aretransferred to chamber 704 and mixed with, in one embodiment, a solidform of bioactive agent 705. Once plunger 701 reaches plunger 702, thecontents can be allowed to mix (although there need not be a pause).Then, plungers 701 and 702 together are advanced towards the front ofchamber 704 thereby extruding the mixture out of the needle 706.

In some embodiments, the contents of chamber 703 can be transferred tochamber 704 by other means than channel 707. In one embodiment, plunger702 can be semi-permeable and then pressure is applied to plunger 701,the contents can be allowed to advance through the semi-permeablemembrane. In another embodiment, a needle can be situated to punctureplunger 702 to allow the contents of chamber 703 to advance into chamber704. Other possible plunger configurations are within the scope of thepresent description.

The Product

The injectable materials comprise one or more biocompatible materials.The materials include, but are not limited to, dermal fillers,hyaluronic acid-based dermal fillers (e.g. Juvederm™ Ultra and Juvederm™Ultra Plus (Allergan, Irvine, Calif.)), hydrogels (i.e. superabsorbentnatural or synthetic polymers), organogels, xerogels, encapsulatedand/or cross-linked biomaterials, silicones, glycosaminoglycans (e.g.chondroitin sulfate, dermatin sulfate, dermatin, dermatin sulfate,heparin sulfate, hyaluronic acid, o-sulfated hyaluronic acid),polysaccharides (e.g. chitosan, starch, glycogen, cellulose), collagen,elastin, local anesthetics (e.g. Benzocaine, Chloroprocaine,Cyclomethycaine, Dimethocaine/Larocaine, Propoxycaine,Procaine/Novocaine, Proparacaine, Tetracaine/Amethocaine, Amino amides,Articaine, Bupivacaine, Carticaine, Cinchocaine/Dibucaine, Etidocaine,Levobupivacaine, Lidocaine/Lignocaine, Mepivacaine, Piperocaine,Prilocaine, Ropivacaine, Trimecaine), drugs, bioactive agents,antioxidants, enzyme inhibitors (e.g. anti-hyaluronidase), vitamins,minerals, water, saline, light curable or light activated materials,vaccines, and pH curable or pH activated materials. Other biocompatiblematerials not mentioned above are also considered within the scope ofthe present description.

The injectable materials may be made up of a first material and a secondmaterial that is mixed with the first material prior to injection, asdescribed elsewhere herein. In some embodiments, the second material isa bioactive agent which facilities delivery of the first duringinjection (e.g. to reduce extrusion force). Additional bioactive agentsmay include anti-proliferatives including, but not limited to, macrolideantibiotics including FKBP-12 binding compounds, estrogens, chaperoneinhibitors, protease inhibitors, protein-tyrosine kinase inhibitors,leptomycin B, peroxisome proliferator-activated receptor gamma ligands(PPARγ), hypothemycin, nitric oxide, bisphosphonates, epidermal growthfactor inhibitors, antibodies, proteasome inhibitors, antibiotics,anti-inflammatories, anti-sense nucleotides and transforming nucleicacids. Drugs can also refer to bioactive agents includinganti-proliferative compounds, cytostatic compounds, toxic compounds,anti-inflammatory compounds, anti-fungal agents, steroids,chemotherapeutic agents, analgesics, antibiotics, protease inhibitors,statins, nucleic acids, polypeptides, growth factors and deliveryvectors including recombinant micro-organisms, liposomes, and the like.Combinations of additional bioactive agents are also within the scope ofthe present description.

Other injectable materials include toxins such as botulinum toxins. Thebotulinum toxin can be selected from the group consisting of botulinumtoxin types A, B, Cl, D, E, F and G, a pure or purified (i.e. about 150kD) botulinum toxin, as well as a native or recombinant botulinum toxin.The material can comprise between about 1 unit to about 20,000 units ofthe botulinum toxin or a therapeutically effective amount, and thecomposition can comprise an amount of botulinum toxin sufficient toachieve a therapeutic effect lasting between 1 month and 5 years. Thebotulinum toxin can be reconstituted within the device as describedelsewhere herein or before the cartridge is placed in the device. Thebotulinum toxin can be reconstituted with sterile 0.9% sodium chloride(saline).

The dilution ratio can be 1 to 100 units of botulinum toxin per 0.1 mLof saline. More preferably, 1 to 50 units per 0.1 mL of saline, or 1 to10 units per 0.1 mL of saline. In one embodiment, 4 units per 0.1 mL ofsaline can be used. The dilution ratio will be highly dependent on thetype of botulinum toxin used or combination of botulinum toxins used.

Additional Features

Power to the device can be supplied by such means as a direct connectionto an AC/DC power source, this can be accomplished using an electricalplug. Using a direct connection to a power source as described aboverequires that the devices be restrained by the power cord. In oneembodiment, the devices are substantially entirely powered by one ormore batteries located in the device shell. The batteries may be commonnon-rechargeable types such as, but not limited to, A, AA, AAA, C, D,and 9V. The one or more batteries used may be rechargeable batteries.The rechargeable battery(s) can be charged through induction or throughdirect-connect interface to an AC/DC power source. In one embodiment,the rechargeable battery(s) may be a permanent battery that chargeswithin the devices and is not removed by the operator. The rechargeablebattery(s) may be semi-permanent meaning they are charged inside thedevices, but can be replaced if the battery(s) expire or malfunctionover time. The rechargeable battery(s) may be operator replaceable ofeither standard or non-standard type batteries. The operator replaceablerechargeable batteries may be charged within the devices or outside thedevices. The operator replaceable rechargeable batteries charged outsidethe devices can be specific for the devices and comprise a series ofstandby batteries ready for rapid swapping.

The devices can comprise one or more means of electronic storage. Thestorage can be built-in internal storage (e.g. random access memory,flash memory, read only memory, microdrive). The internal storage may bebuilt directly into the PCB. The storage can be an external source. Thedevice can comprise a slot to which an external storage device may beconnected or inserted. Such external storage devices include, but arenot limited to universal serial bus (USB) drives, firewire drives, flashand media cards, and microdrives.

The internal or external storage can contain information about thedevice and/or the cartridge or product associated with the device. Theinformation can include, but is not limited to, operating software,firmware, device usage statistics, patient information, patient name,patient identification, Product name, Product part number, Product Rxnumber, Product lot number, Product expiration date, date ofinjection(s), time of injection(s), area(s) of injection(s), injectionvolume(s), injection volume(s) per area injected, total volume injected,and operator name.

The devices may further comprise a stand (not shown). The stand canfunction as a convenient place to store the device when it is not inuse. The stand may further be used to charge the device. A single standmay comprise multiple devices. The stand can further comprise a port(e.g. USB, firewire) from which data can be transferred to and from thedevice's internal or external storage or devices housed in the stand.The data can be synchronized with database software stored on astandalone or networked computer. The stand may further comprise thecomponents to wirelessly network the injection device and its datacontents for retrieval wirelessly throughout a network.

The devices can be fitted with a power speaker driven by the powersource and controlled by the PCB. The speaker can produce audible toneswhen the device needs attention. Such instances that may requireattention include, but are not limited to, low battery power, emptycartridge, confirmation of a setting, power on and power off

The devices may have an outer tip that can come into contact with thepatient's skin at the future site of injection. The tip may be cooled,thereby reducing the pain associated with needle punctures through theskin. The tip can be made of a metal or metal alloy. The cool touch ofmetal alone may be all that is required to reduce the pain associatedwith a needle puncture, but more extreme cooling may be required.Methods of cooling are known in the art and may include liquid nitrogenand/or a Peltier device.

The devices described herein can further comprise at least one lightsource. The light source may be fixed or adjustable. In one embodiment,the light source can be a source of visible light such as an LED, toassist the operator in viewing the site of injection. In one embodiment,the light source is ultraviolet (UV). UV light can be used to cure oractivate the Product that has been injected into the skin. Thewavelength of UV light used can be determined by the operator dependingon the absorption spectrum of the Product being injected. In oneembodiment, the light may be produced by a laser, such as a laserpointer. The laser pointer light can assist an operator in preciselycontrolling the location of the injection.

The injection devices described herein can inject materials that aredifficult or even impossible to inject manually using a conventionalsyringe and plunger due to the high extrusion forces necessary to injectthem. The present devices are capable of injecting such materials in ahighly controlled, precise manner through a various range of needlegauges. The needle gauge can be at least 10 G to as high as 50 G. Forexample, the needle gauge may be a gauge in a range of between about 23G to about 34 G, for example, between about 27 G to about 32 G. Thedevices can deliver Product at a rate of about 0.001 to about 1 mL/sec.More preferable injection speeds can be between 0.004 to 0.05 mL/sec.The rate of delivery is highly dependent of the viscosity of the Productbeing delivered and the density of the tissue being injected. Generally,a highly viscous Product will require a higher extrusion force relativeto a required extrusion force for a relatively lower viscosity Product.The devices described herein can inject the material, for example, atthe desired rate, with extrusion forces of at least about 50 Newtons (N)and up to about 200 N.

FIG. 9 depicts a logic diagram of the internal components in anexemplary embodiment of the invention.

The device components may include a charging dock connector 901,charging integrated circuitry 902 which manages the charging anddischarging of the battery 903, for example a rechargeable lithium-ioncell battery, which is the main power source for the device, and reportsstatus changes to the programmable microcontroller 904. A 3.0V powersupply 906, provides power for the circuitry. A boost converter 908creates 5V that is used to drive the motor 910. H Bridge 909 controlsthe speed and direction of the motor 910, for example a DC motor, whichis used to drive the piston in the cartridge (piston and cartridge notshown in FIG. 9). A backlight driver 914 activates a backlight on theliquid crystal display screen 916. Buttons 918 allow for user input, forexample, of a desired injection rate. A product identifier 920 reads thecartridge (not shown) as described elsewhere herein, and throughmicrocontroller 904, notifies the user of the product in the cartridge.In an exemplary embodiment, buttons 918 include a pressure sensitiveswitch, for example, a commercially available, a thin, flexiblepiezoresistive force sensor called FlexiForce model no. A201 in the 0-25lb (110 N) force range, manufactured by Tekscan.

The components can work together to sense cartridges that are insertedinto the device. The device can include sensors (as described infra)capable of detecting correct insertion of different types of injectioncartridges. The cartridges can be marked by features such as bumps,flags, light and dark lines, or other means known in the art.

The device may have the ability to drive a motor at variable speeds tofacilitate different rates of delivery of the Product. Themicrocontroller can have the ability to run the motor in both rotationaldirections. Additionally, the device may have sensors to quantify thevelocity of the drive train and verify the desired delivery rate. Thesensors may provide feedback to the microcontroller allowing it to drivethe motor faster or slower if the desired delivery rate is not beingmet.

In one embodiment, upon actuation of the inject button, a signal can besent to the microcontroller and therein the software may drive the motorforward at the proper velocity for the desired injection rate. Thesoftware can implement one or more algorithms to maintain the injectionrate during variations in resistance from the cartridge and/or the drivetrain.

In one embodiment, upon release of the inject button, the software andmicrocontroller shall drive the motor in reverse to full speed for apredetermined distance in order to release the pressure on thecartridge. This can allow for more precise delivery of Product and canprevent leaking.

In one embodiment, in the event that the microprocessor detects theentire contents of the cartridge have been expelled, the microprocessorcan reverse the motor as described above and present an “emptycartridge” warning on the display.

In one embodiment, upon detection by the microprocessor, based onfeedback from sensors, that the desired injection rate cannot beattained, the motor may reverse as though the inject button wasreleased, and a warning message may be displayed. This situation couldresult from situations such as, but not limited to, an improperlyinserted cartridge, a blockage preventing delivery of the Product, amechanical failure or combinations thereof.

In some embodiments, the devices described herein can deliver Productsor inject into areas of tissue that require high precision. As such, thedevices can have one or more, in some cases two or more, sensors whichmonitor the device's precision. In some embodiments, the sensors orsystems can be redundant.

In some embodiments, the Products to be delivered may be non-Newtonianor mixtures of Newtonian and non-Newtonian fluids. Such fluids can haveinconsistent and/or unpredictable force-to move requirements which mayutilize the redundant features described above. Such products can havehigh yield points requiring high stall torque requirements.Non-Newtonian fluids may have high yield points but have rapid drops inforce-to-move requirements after the yield point is overcome. As such,the devices described herein can accommodate for rapid changes inextrusion force requirements.

In one embodiment, the devices can achieve a steady state of materialdelivery despite the changes in fluid consistency and/or viscosity,including differing yield points. Additionally, in some embodiments, twoor more different materials can be utilized requiring enough force toovercome two or more different yield points at two or more differenttimes during injection. As such, the devices can be equipped withelectronics that can constantly monitor the delivery force, speed, andcartridge pressure to name a few. In addition, those devices may bedesigned such that the plunger may be backed up at the termination ofproduct dispensation in order to avoid over-dispensing Product due to,for example, pressure build up in the Product cartridge duringadministration.

FIG. 10 depicts non-limiting display screen variations that may be usedwith the devise described herein. In one embodiment, a welcome screen isdisplayed. In another embodiment, the display screen can instruct theoperator to insert a cartridge or even to reinsert a cartridge if it isnot inserted correctly. In one embodiment, if the device is using acartridge that requires reconstitution, the display screen may instructthe operator to reconstitute the Product or to insert the device in itsbase for reconstitution of the Product. In one embodiment, the displayscreen can display information prior to, during and after injectionshowing such information as, but not limited to, product name, number ofunits injected, current, past and present injection speeds, and batterylife. In one embodiment, when the device is placed in its base, it canbe charged and the display can indicate the device is being charged.

FIG. 11 depicts a non-limiting combination of internal components 1100housed in the inner body of a device as described herein. One skilled inthe art will appreciate that the components may be situated differentlydepending on the configuration of the inner body and/or the shape of theouter body of the device. In one embodiment, the internal components ofFIG. 11 may be used in conjunction with the device in FIG. 8.Combination of internal components 1100 comprises a motor 1120 whichturns worm gear 1118, thereby driving rack 1102. Rack 1102 engages theplunger (not shown) in posterior end 1105 of cartridge 1101. PCB 1110can gather and send information to optical encoder 1116, microswitch1114, cartridge locking/ejection mechanism 1108, and screen 1104. ThePCB 1110 and screen 1104 are powered by battery 1112. In one embodiment,optical encoder 1116 can accurately determine the position, speed anddirection of the rack 1102 by counting the number of turns and turndirection of motor shaft 1119. In one embodiment, microswitch 1114 isactivated when lever arm 1107 is flexed downward and makes contact withmicroswitch 1114. Lever arm 1107 is flexed downward every time it passesover cartridge detent 1106 until cartridge 1101 is fully inserted andengaged into locking/ejection mechanism 1108. The number of cartridgedetents can vary, depending on the type of product and/or product volumein cartridge 1101. The number of microswitch activations is relayed toPCB 1110 and PCB 1110 identifies the cartridge inserted. When cartridge1101 is identified, PCB 1110 communicates this information to motor 1120to drive rack 1102 to the appropriate starting location and also to thedisplay on screen 1104 to inform the operator of the product type (name)and initial (or remaining) product volume. In one embodiment, cartridge1101 is unlocked and is partially ejected from the device when the usersimultaneously presses both eject buttons 1109 (only one shown) ofcartridge locking/ejection mechanism 1108. This generally occurs afterthe user has injected the full contents of the cartridge.

EXAMPLE 1

Extrusion experiments were performed on 0.8 mL Schott TopPac® (SCHOTTNorth America, Inc., Lebanon, Pa.) syringe fitted with a Tyco 30 G×½″needle. Juvèderm™ Ultra (Allergan Inc., Irvine, Calif.) was extrudedfrom the needle to assess the force needed to extrude the highly viscoushyaluronic acid-based dermal filler through a 30 G needle. The resultsin Table 1 show the results of the experiments.

TABLE 1 Approximate Plunger Rate Plunger Rate Injection Rate*Approximate Force (mm/min) (mm/sec) (mL/sec) Required (N) 20 0.333 0.00623 50 0.833 0.015 35 100 1.667 0.029 47 150 2.500 0.044 60 *Schott 0.8mL syringe the gradient is: 5.7 mm is approximately 0.1 mL

For example, to inject the total contents of the syringe at a rate of0.006 mL/sec, the plunger must travel approximately 46 mm in a time ofapproximately 2.3 min (approximate plunger rate of 20 mm/min).

Results showed that depending on the desired injection rate, largeforces are required to advance the plunger and inject the viscous dermalfiller. It is quite easy to see why manual injection with a traditionalplunger style syringe would be quite difficult to control and inject atthe same time. The device described herein can provide the appropriateforce for a given injection speed while eliminating operator error ininjection and patient pain associated with it.

EXAMPLE 2

This example refers to the device 100 depicted in FIGS. 1A-1C, theelectronic display screen 400 in FIG. 4, and the injection components ofthe inner body depicted in FIG. 5.

The operator turns on the device 100 by depressing power button 105. Theelectronic display 106 (which may comprise screen 400 in FIG. 4) willpower on and indicate the device status as ‘cartridge not loaded.’ Thedevice is then set-up to provide an audible beep to alert the operatoras to the status ‘cartridge not loaded.’ The operator proceeds to slidethe cartridge into the hole at the front of the device in cap 107. Thehole in cap 107 reveals the cartridge chamber in the inner body of thedevice. The cartridge is slid into the device until it clicks in place.The device then reads the RFID off the cartridge and presents theappropriate data on display 106. Once the data is uploaded from the RFIDand processed by the device, ‘Ready’ will be presented on display 106.The operator can then adjust the injection speed by using a combinationof + and − buttons 103 and 104, or through the menu driven multi-button108. If using buttons 103 and 104, the injection speed can be changedeven during the injection. If the menu driven multi-button 108 is used,the speed of injection must be selected in the menu and must be setusing multi-button 108 and confirmed using button 109. Thereafter, thespeed of the injection cannot be changed during the injection.

The operator then installs an appropriate needle 112 onto the luer-tip113 at the exposed end of the cartridge. The sheath around the needle isthen removed. The area for injection is cleaned appropriately. Theneedle is punctured through the skin at the appropriate location of apatient and inject button 102A or 102B is pressed. The Product isdispensed from the device and an audible beep signals the operator thatthe injection is complete. The needle is removed from the patent anddiscarded appropriately. The needle and cartridge can be ejected fromthe device safely by pressing eject button 110, thereafter, thecartridge and needle will fall from the device as a single unit(preferably into an appropriate biohazard container) when the device isangled downward. The operator can then power the device off by pressingand holding power button 105.

EXAMPLE 3

This example refers to the device 100 depicted in FIGS. 1A-1C, theelectronic display screen 400 in FIG. 4, and the components of the innerbody depicted in FIG. 6.

The operator turns on the device 100 by depressing power button 105. Ared LED illuminates indicating the device is not ready for injection.The electronic display 106 will power on and indicate the device statusas ‘cartridge not loaded.’ The device can be set-up to provide anaudible beep to alert the operator as to the status ‘cartridge notloaded.’ The operator proceeds to slide a cartridge of dried botulinumtoxin Type A into the hole at the front of the device in cap 107. Thehole in cap 107 reveals the cartridge chamber in the inner body of thedevice. The cartridge is slid into the device until it clicks in place.The device then reads the RFID off the cartridge and presents theappropriate data on display 106. Once the data is uploaded from the RFIDand processed by the device, the device indicates to the operator thatsaline needs to be loaded, by displaying ‘load saline vial’ on display106. The operator loads a saline vial into the device through a separateopening in the device until it snaps into place.

Then, display 106 indicates ‘adjust dose setting.’ The operator inputsthe appropriate dose using multi-button 108 and locks in the dose usingset button 109. Then, display 106 will indicate ‘reconstitute product’.The operator depresses set button 109 on the device. The devicereconstitutes the botulinum toxin and gently mixes it for apredetermined amount of time. Thereafter, the red LED with turn greenindicating the Product is ready for injection and ‘ready’ will bepresented on display 106. The operator can then adjust the injectionspeed by using a combination of buttons 103 and 104, or through the menudriven multi-button 108. If using buttons 103 and 104, the injectionspeed can be changed even during the injection. If the menu drivenmulti-button 108 is used, the speed of injection must be selected in themenu and must be set using set button 109. Thereafter, the speed of theinjection cannot be changed during the injection.

The operator then installs an appropriate needle 112 onto the luer-tip113 at the exposed end of the cartridge. The sheath around the needle isthen removed. The area for injection is cleaned appropriately. Theneedle is punctured through the skin at the appropriate location of apatient and inject button 102A or 102B is pressed. The Product isdispensed from the device and an audible beep signals the operator thatthe injection is complete. The needle is removed from the patent anddiscarded appropriately. The needle and cartridge can be ejected fromthe device safely by pressing eject button 110, thereafter, thecartridge and needle will fall from the device as a single unit(preferably into an appropriate biohazard container) when the device isangled downward. The operator can then power the device off by pressingand holding power button 105.

EXAMPLE 4

This example refers to the device 800 depicted in FIG. 8, the electronicdisplay screen in FIG. 4, the cartridge in FIG. 7 and the injectioncomponents of the inner body depicted in FIG. 5.

The operator turns on the device by holding down power/select button805. A red LED illuminates indicating the device is not ready forinjection. The electronic display 806 will power on and indicate thedevice status as ‘cartridge not loaded.’ The device can be set-up toprovide an audible beep to alert the operator as to the status‘cartridge not loaded.’ The operator proceeds to slide a multi-chambercartridge as seen in FIG. 7 into the hole at the front of the device.The hole at the front of the device reveals the cartridge chamber in theinner body of the device. The cartridge is slid into the device until itclicks in place. The device then reads the RFID off the cartridge andpresents the appropriate data on display 806. Once the data is uploadedfrom the RFID and processed by the device, the device indicates to theoperator that the saline needs to be gently mixed into the lyophilizedbotulinum toxin Type A by showing ‘ready to reconstitute’ on display806. The operator pushes power/select button 805 to accept the requestand the saline is gently mixed into the lyophilized botulinum toxin.After mixing is completed and the appropriate time has elapsed, thedisplay 806 reads ‘adjust dose setting.

The operator inputs the appropriate dose using multi-button 807 andlocks in the dose using power/select button 805. Thereafter, the red LEDwith turn green indicating the Product is ready for injection and‘ready’ will be presented on display 806. The operator can then adjustthe injection speed by using a combination of multi-button 807 andpower/select button 805.

The operator then installs an appropriate needle 808 onto the luer-tipat the exposed end of the cartridge 809. The sheath around the needle isthen removed. The area for injection is cleaned appropriately. Theneedle is punctured through the skin at the appropriate location of apatient and inject button 802 or 803 is pressed. The Product isdispensed from the device and an audible beep signals the operator thatthe injection is complete. The needle is removed from the patent anddiscarded appropriately. The needle and cartridge can be ejected fromthe device safely by pressing eject button 804, thereafter, thecartridge and needle will fall from the device as a single unit(preferably into an appropriate biohazard container) when the device isangled downward. The operator can then power the device off by holdingdown power/select button 805.

Unless otherwise indicated, all numbers expressing quantities ofingredients, properties such as molecular weight, reaction conditions,and so forth used in the specification and claims are to be understoodas being modified in all instances by the term “about.” Accordingly,unless indicated to the contrary, the numerical parameters set forth inthe specification and attached claims are approximations that may varydepending upon the desired properties sought to be obtained by thepresent invention. At the very least, and not as an attempt to limit theapplication of the doctrine of equivalents to the scope of the claims,each numerical parameter should at least be construed in light of thenumber of reported significant digits and by applying ordinary roundingtechniques. Notwithstanding that the numerical ranges and parameterssetting forth the broad scope of the invention are approximations, thenumerical values set forth in the specific examples are reported asprecisely as possible. Any numerical value, however, inherently containscertain errors necessarily resulting from the standard deviation foundin their respective testing measurements.

The terms “a,” “an,” “the” and similar referents used in the context ofdescribing the invention (especially in the context of the followingclaims) are to be construed to cover both the singular and the plural,unless otherwise indicated herein or clearly contradicted by context.Recitation of ranges of values herein is merely intended to serve as ashorthand method of referring individually to each separate valuefalling within the range. Unless otherwise indicated herein, eachindividual value is incorporated into the specification as if it wereindividually recited herein. All methods described herein can beperformed in any suitable order unless otherwise indicated herein orotherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (e.g., “such as”) provided herein isintended merely to better illuminate the invention and does not pose alimitation on the scope of the invention otherwise claimed. No languagein the specification should be construed as indicating any non-claimedelement essential to the practice of the invention.

Groupings of alternative elements or embodiments of the inventiondisclosed herein are not to be construed as limitations. Each groupmember may be referred to and claimed individually or in any combinationwith other members of the group or other elements found herein. It isanticipated that one or more members of a group may be included in, ordeleted from, a group for reasons of convenience and/or patentability.When any such inclusion or deletion occurs, the specification is deemedto contain the group as modified thus fulfilling the written descriptionof all Markush groups used in the appended claims.

Certain embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention. Ofcourse, variations on these described embodiments will become apparentto those of ordinary skill in the art upon reading the foregoingdescription. The inventor expects skilled artisans to employ suchvariations as appropriate, and the inventors intend for the invention tobe practiced otherwise than specifically described herein. Accordingly,this invention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

Furthermore, numerous references have been made to patents and printedpublications throughout this specification. Each of the above-citedreferences and printed publications are individually incorporated hereinby reference in their entirety.

In closing, it is to be understood that the embodiments of the inventiondisclosed herein are illustrative of the principles of the presentinvention. Other modifications that may be employed are within the scopeof the invention. Thus, by way of example, but not of limitation,alternative configurations of the present invention may be utilized inaccordance with the teachings herein. Accordingly, the present inventionis not limited to that precisely as shown and described.

1-10. (canceled)
 11. A hand-held injection device comprising: acartridge suitable containing a dermal filler; a shell configured tosupport the cartridge; a motorized drive mechanism; a power source foractivating the drive mechanism; and a plunger actuated by the drivemechanism for urging the dermal filler out of the cartridge.
 12. Thedevice of claim 11, further comprising a user-programmable controllercoupled to the drive mechanism and configured to be set at auser-defined injection rate.
 13. The device of claim 12, wherein theuser-defined injection rate can be set at a rate between about 0.001mL/sec and about 1 mL/sec.
 14. The device of claim 11, furthercomprising a needle coupled to a distal end portion of the cartridge,wherein the plunger is configured to urge the dermal filler out of thecartridge through the needle.
 15. The device of claim 11, wherein theshell comprises a U-shaped appendage configured to receive a finger ofan operator, the shell further comprising an injection button disposedon a top side of the shell.
 16. The device of claim 11, wherein theshell has a pistol-grip style design in which the shell has alongitudinal body and a grip extending from a lateral side of thelongitudinal body.
 17. The device of claim 11, further comprising a vialcoupled to the cartridge for providing a dilutant for mixing with thedermal filler during delivery of the dermal filler.
 18. A hand-heldinjection device comprising: a cartridge containing a dermal filler andhaving a distal end portion configured to be coupled to a needle; anouter shell configured to support the cartridge and be held by anoperator; a plunger coupled to the cartridge for urging the dermalfiller from within the cartridge out through the needle; a motorizeddrive mechanism comprising a motor and a gear, the motorized drivemechanism being coupled to the plunger for driving motion of theplunger; and a power source configured to activate the motorized drivemechanism.
 19. The device of claim 18, further comprising auser-programmable controller coupled to the motorized drive mechanismand configured to be set at a user-defined injection rate.
 20. Thedevice of claim 19, wherein the user-defined injection rate can be setat a rate between about 0.001 mL/sec and about 1 mL/sec.
 21. The deviceof claim 18, wherein the shell comprises a U-shaped appendage configuredto receive a finger of the operator, the shell further comprising aninjection button disposed on a top side of the shell.
 22. The device ofclaim 18, wherein the shell has a pistol-grip style design in which theshell has a longitudinal body and a grip extending from a lateral sideof the longitudinal body.
 23. The device of claim 18, further comprisinga vial coupled to the cartridge for providing a dilutant for mixing withthe dermal filler during delivery of the dermal filler.
 24. A hand-heldinjection device comprising: a cartridge containing a dermal filler; avial coupled to the cartridge for providing a dilutant for mixing withthe dermal filler in the cartridge; a plunger configured to urge thedermal filler out of the cartridge; and a motor configured to agitatethe mixture in the cartridge.
 25. The device of claim 24, furthercomprising a motorized drive mechanism and a user-programmablecontroller coupled to the motorized drive mechanism for setting auser-defined injection rate.
 26. The device of claim 25, wherein theuser-defined injection rate can be set at a rate between about 0.001mL/sec and about 1 mL/sec.
 27. The device of claim 25, furthercomprising a power source configured to activate the motorized drivemechanism.
 28. The device of claim 24, further comprising a shellconfigured to support the cartridge, wherein the shell is elongate andconfigured to be held by an operator in a similar manner to that of awriting instrument.
 29. The device of claim 28, wherein the shellcomprises a U-shaped appendage configured to receive a finger of anoperator, the shell further comprising an injection button disposed on atop side of the shell.
 30. The device of claim 24, further comprising ashell configured to support the cartridge, wherein the shell has apistol-grip style design in which the shell has a longitudinal body anda grip extending from a lateral side of the longitudinal body.